title: Targeting the ubiquitin-proteasome system for cancer therapy.
abstract: BACKGROUND
  The ubiquitin-proteasome system (UPS) degrades 80 - 90% of intracellular proteins. Cancer cells take advantage of the UPS for their increased growth and decreased apoptotic cell death. Thus, the components that make up the UPS represent a diverse group of potential anti-cancer targets. The success of the first-in-class proteasome inhibitor bortezomib not only proved that the proteasome is a feasible and valuable anti-cancer target, but also inspired researchers to extensively explore other potential targets of this pathway.
  
  
  METHODS
  This review provides a broad overview of the UPS and its role in supporting cancer development and progression, especially in aspects of p53 inactivation, p27 turnover and NF-κB activation. Also, efforts toward the development of small molecule inhibitors (SMIs) targeting different steps in this pathway for cancer treatment are reviewed and discussed.
  
  
  CONCLUSIONS
  Whereas some of the targets in the UPS, such as the 20S proteasome, Nedd8 activating enzyme and HDM2, have been well-established and validated, there remains a large pool of candidates waiting to be investigated. Development of SMIs targeting the UPS has been largely facilitated by state-of-the-art technologies such as high-throughput screening and computer-assisted drug design, both of which require a better understanding of the targets of interest.
authors.affiliation: Wayne State University, Barbara Ann Karmanos Cancer Institute, School of Medicine, Department of Pharmacology, Detroit, MI 48201, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Shen
authors.forename: Sara
authors.initials: S
authors.lastname: Schmitt
authors.forename: Daniela
authors.initials: D
authors.lastname: Buac
authors.forename: Q Ping
authors.initials: QP
authors.lastname: Dou
mesh_terms: D000818:Animals; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex